The present invention relates to a new combination of drugs for the prophylaxis and therapy of prostate hyperplasia.
Prostate hyperplasia is a benign enlargement of the prostate beginning from the so-called "inner" prostate. The attendant complaints are due primarily to the resultant obstructions of the urethra. Voiding is made difficult and retention of urine residue occurs. Without surgical interference, uremia can ensue.
Heretofore, it has hardly been possible to medicinally treat this disease, occurring with great frequency in older men. The phyto-preparations tested for this purpose, e.g., .beta.-sitosterol, mixtures of various plant extracts, and combinations of plant extracts with the neutropic spasmolytic azoniaspirochloride have proved ineffective as determined by a one-year study. Although the patients in this study experienced an improvement in miction symptoms, under therapy, an involution of the hyperplastic prostate was not achieved.
Hormones have likewise been utilized in the treatment of prostate hyperplasia. Among these compounds, the depot progestogen gestonorone caproate deserves particular mention. As compared to the phyto-preparations, a better effect is obtained with gestonorone caproate. The miction period, prolonged prior to treatment, is markedly shortened, and the maximum flow value (flow of urine per unit time) is improved. A marked reduction of the size of the adenoma, however, also cannot be achieved with this compound.
In U.S. Pat. No. 3,423,507, a treatment of prostate hypertrophy is described. It involves use of the progestationally and anti-androgenically effective esters of 6-chloro-17-hydroxy-1.alpha.,2.alpha.-methylenepregna-4,6-diene-3,20-dione (cyproterone esters). However, it was found that even under this treatment there is only a partial retrogression of hyperplasia.
In prostate hyperplasia, the fibromuscular proportion of the prostate (interstitium) proliferates primarily. A possible cause for this, inter alia, is a shift in the estrogen/androgen ratio in favor of the estrogens. It has been found in various investigations that, in older men, the serum testosterone concentrations are reduced; at the same time, the proportion of SHBG (sex hormone binding globuline, specific transport protein for steroids) increases, so that the biological availability of androgens is even further reduced.
In the conventional laboratory animal species, only older dogs experience spontaneous prostate hyperplasia comparable to the changes caused in males by prostate hyperplasia. Also in the dog, there is a proliferation primarily of the fibromuscular portion of the prostate. It is also possible to cause the aspects of the disease in younger dogs by treatment with an estrogen or an estrogen/androgen mixture. Our own experiments have shown that the additional treatment with anti-androgen (cyproterone acetate) leads to total atrophy of the gland parenchyma, but that the proliferation of the interstitium is not affected.
In autoradiographic studies on human prostate hyperplasia tissue, it has furthermore been shown that only the gland epithelium (parenchyma) is a target organ for androgens, rather than the interstitium. Additionally, it was discovered that fibroblast cultures from human prostata hyperplasia tissue aromatize testosterone about seven to nine times more strongly to estrogens than fibroblast cultures derived from healthy prostata tissue.